Molecular Anatomy of the Developing Human Retina

• Published in: Developmental cell Vol. 43; no. 6; pp. 763 - 779.e4
• Main Authors: Hoshino, Akina, Ratnapriya, Rinki, Brooks, Matthew J., Chaitankar, Vijender, Wilken, Matthew S., Zhang, Chi, Starostik, Margaret R., Gieser, Linn, La Torre, Anna, Nishio, Mario, Bates, Olivia, Walton, Ashley, Bermingham-McDonogh, Olivia, Glass, Ian A., Wong, Rachel O.L., Swaroop, Anand, Reh, Thomas A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 18.12.2017
• Subjects: Animals; development; Eye Proteins - genetics; Eye Proteins - physiology; fetal; fovea; Fovea Centralis - embryology; Gene Expression Regulation, Developmental; gene network; Gene Regulatory Networks; human; Humans; macula; Macula Lutea - embryology; Mice; Morphogenesis; Neurogenesis - genetics; Neurogenesis - physiology; Neurons - metabolism; organoids; photoreceptor; retina; Retina - cytology; Retina - embryology; Retina - growth & development; Retina - physiology; Sequence Analysis, RNA - methods; Transcriptome; development; retina; transcriptome; organoids; photoreceptor; fovea; gene network; human; fetal; macula
• ISSN: 1534-5807; 1878-1551; 1878-1551
• DOI: 10.1016/j.devcel.2017.10.029

Clinical and genetic heterogeneity associated with retinal diseases makes stem-cell-based therapies an attractive strategy for personalized medicine. However, we have limited understanding of the timing of key events in the developing human retina, and in particular the factors critical for generating the unique architecture of the fovea and surrounding macula. Here we define three key epochs in the transcriptome dynamics of human retina from fetal day (D) 52 to 136. Coincident histological analyses confirmed the cellular basis of transcriptional changes and highlighted the dramatic acceleration of development in the fovea compared with peripheral retina. Human and mouse retinal transcriptomes show remarkable similarity in developmental stages, although morphogenesis was greatly expanded in humans. Integration of DNA accessibility data allowed us to reconstruct transcriptional networks controlling photoreceptor differentiation. Our studies provide insights into human retinal development and serve as a resource for molecular staging of human stem-cell-derived retinal organoids. •Transcriptomes of developing human retina reveal compartmentalized neurogenesis•Fovea differentiation, including lamination, is complete long before nasal retina•Combined RNA-seq and DNase analysis reveals developmental regulatory networks•Provides a reference for molecular staging of retinal organoids from human stem cells Hoshino et al. describe transcriptome dynamics and spatiotemporal analyses of developing human retina, demonstrating distinct periods of neurogenesis in the fovea versus nasal retina. Comparison with mouse retinal transcriptomes and integration with open chromatin datasets reveal evolutionary conservation of developmental regulatory networks and unique characteristics of human retinal differentiation.